2. Immunology/Inflammation PROTAC Autophagy
  3. NOD-like Receptor (NLR) ATTECs Autophagy
  4. MC-ND-18

MC-ND-18 is an ATTEC degrader that degrades NLRP3 via the Autophagy pathway, with a DC50 of 125.5 nM in THP-1 cells. MC-ND-18 exhibits anti-inflammatory activity in a DSS-induced mouse model of colitis. MC-ND-18 can be used for research on inflammatory bowel disease. MC-ND-18 consists of an NLRP3 inhibitor (HY-156121), a linker (HY-W018745), and an LC3 ligand.

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MC-ND-18

MC-ND-18 Chemical Structure

CAS No. : 3081572-53-1

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Based on 1 publication(s) in Google Scholar

MC-ND-18 Related Antibodies

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Description

MC-ND-18 is an ATTEC degrader that degrades NLRP3 via the Autophagy pathway, with a DC50 of 125.5 nM in THP-1 cells. MC-ND-18 exhibits anti-inflammatory activity in a DSS-induced mouse model of colitis. MC-ND-18 can be used for research on inflammatory bowel disease. MC-ND-18 consists of an NLRP3 inhibitor (HY-156121), a linker (HY-W018745), and an LC3 ligand[1].

IC50 & Target[1]

NLRP3

125.5 nM (DC50)

In Vitro

MC-ND-18 (100-200 nM; 24 h) potently inhibits IL-1β secretion in PMA-differentiated THP-1 cells, with an inhibition rate of 73.6% at 200 nM and 45.8% at 100 nM[1].
MC-ND-18 (100-500 nM; 24 h) induces concentration-dependent degradation of NLRP3 in PMA-differentiated THP-1 cells, with degradation rates of 65% at 500 nM, 49% at 200 nM, and 13% at 100 nM[1].
MC-ND-18 (50 nM-1 μM; 24 h) induces NLRP3 degradation in PMA-differentiated THP-1 cells, with a DC50 of 125.5 nM, and the maximum degradation rate reaches up to 70% at 500 nM[1].
MC-ND-18 (50 nM-5 μM; 24 h) exhibits low cytotoxicity in PMA-differentiated THP-1 cells, and no significant reduction in relative cell viability is observed after incubation at concentrations ranging from 50 nM to 5 μM for 24 h[1].
MC-ND-18 (19.5 nM-5 μM) binds to purified NLRP3 protein lacking the LRR domain and LC3B protein, with Kd values of 0.929 μM and 3.548 μM, respectively, indicating that it exhibits concentration-dependent affinity for both targets[1].
MC-ND-18 (24 h) does not degrade NLRP3 in PMA-differentiated THP-1 cells via the proteasomal pathway, as combined treatment with the proteasome inhibitor MG132 does not attenuate its degrading activity[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

MC-ND-18 Related Antibodies

ELISA Assay[1]

Cell Line: PMA-differentiated THP-1 cells
Concentration: 100 nM, 200 nM
Incubation Time: 24 h (co-incubation with LPS)
Result: Inhibited IL-1β secretion by 45.8 % at 100 nM.
Inhibited IL-1β secretion by 73.6 % at 200 nM.

Western Blot Analysis[1]

Cell Line: PMA-differentiated THP-1 cells
Concentration: 100 nM, 200 nM, 500 nM
Incubation Time: 24 h (co-incubation with LPS)
Result: Degraded NLRP3 by 13 % at 100 nM.
Degraded NLRP3 by 49 % at 200 nM.
Degraded NLRP3 by 65 % at 500 nM.

Western Blot Analysis[1]

Cell Line: PMA-differentiated THP-1 cells
Concentration: 50 nM, 100 nM, 200 nM, 500 nM, 1000 nM
Incubation Time: 24 h (co-incubation with LPS)
Result: Exhibited a concentration-dependent NLRP3 degradation profile from 50 nM to 500 nM.
Achieved a maximum degradation rate of 70 % at 500 nM.
Had a DC50 for NLRP3 degradation of 125.5 nM.
Showed reduced degradation efficiency at 1000 nM, consistent with a "hook effect" for bifunctional molecules.

Immunofluorescence[1]

Cell Line: THP-1 cells
Concentration: 500 nM
Incubation Time: 4 h
Result: Resulted in substantial colocalization of NLRP3 and LC3B, with a Pearson correlation coefficient of 0.53.
Parmacokinetics
Species Dose Route T1/2 Cmax AUC0-t AUC0-∞ F Vz CL Vss
Mice[1] 5 mg/kg i.v. 0.94 h / 2960 ng·h/mL 2966 ng·h/mL / 2.31 L/kg 28.4 mL/min/kg 0.39 L/kg
Mice[1] 5 mg/kg i.p. 1.26 h 555 ng/mL 551 ng·h/mL 562 ng·h/mL 19.0 % / / /
In Vivo

MC-ND-18 (5-20 mg/kg; i.p.; daily) dose-dependently alleviates DSS-induced colitis in C57BL/6 mice, reducing NLRP3 and IL-1β protein levels in colon tissue[1].
MC-ND-18 (20 mg/kg; i.p.; daily) fails to alleviate DSS-induced colitis in NLRP3KO mice, confirming its therapeutic effects are dependent on the NLRP3 pathway[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: C57BL/6 (group size n=5 per cohort)[1]
Dosage: 5 mg/kg; 20 mg/kg
Administration: i.p.; daily
Result: Reduced weight loss and dose-dependent suppression of DAI increase compared to the model group.
Mitigated colon shortening relative to the model group.
Markedly reduced intestinal mucosal damage, inflammatory cell infiltration, and loss of intestinal crypts compared to the model group.
Significantly reduced colonic NLRP3 and IL-1β protein levels compared to the model group.
Animal Model: C57BL/6-NLRP3KO (group size n=3 per cohort)[1]
Dosage: 20 mg/kg
Administration: i.p.; daily
Result: Did not reduce body weight loss, suppress DAI increase, or mitigate colon shortening compared to the model group.
Showed no significant improvement in intestinal mucosal damage, inflammatory cell infiltration, or intestinal crypt loss compared to the model group.
Did not reduce colonic IL-1β levels compared to the model group; NLRP3 protein was undetectable in all cohorts.
Molecular Weight

1051.58

Formula

C42H42Br2IN3O9S
CAS No.
SMILES

IC1=CC=C(C(/C(C2=O)=C/C3=CC(Br)=C(O)C(Br)=C3)=C1)N2CCOCCOCCOCCOC4=CC=C(S(NC(NC5=C6C(CCC6)=CC7=C5CCC7)=O)(=O)=O)C=C4
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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MC-ND-18 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

MC-ND-183081572-53-1NOD-like Receptor (NLR)ATTECsAutophagyAutophagosome-tethering compoundsautophagic mechanismsPMA-differentiated THP-1 cellsmouse model of dextran sulfate sodium-induced colitisdextran sulfate sodium-induced colitisIL-1βNLRP3LC3Bproteasome pathwayC57BL/6 miceautophagic pathwayInhibitorinhibitorinhibit

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